Children account for a significant proportion of U.S. travelers visiting overseas destinations,1 but there are limited data regarding compliance with preventive measures, exposures, and self-limited diseases such as traveler’s diarrhea (TD) which rarely result in a medical evaluation.2,3 The TravMil study (Deployment and Travel Related Infectious Disease Risk Assessment, Outcomes, and Prevention Strategies Among Department of Defense [DoD] Beneficiaries) prospectively evaluates infectious disease risks in DoD beneficiaries traveling outside the continental United States for ≤ 6.5 months.4 We used the TravMil cohort to evaluate differences in pretravel care, compliance with preventive measures, exposures, and illnesses among pediatric and adult military dependents.
Consenting adult and pediatric travelers were enrolled pretravel at four U.S. military travel clinics. Adults were enrolled between 2010 and 2016 at the Naval Medical Center Portsmouth (NMCP), Portsmouth, VA; San Antonio Military Medical Center, San Antonio, TX; Naval Medical Center San Diego (NMCSD), San Diego, CA; and Walter Reed National Military Medical Center, Bethesda, MD. Pediatric subjects were enrolled between 2010 and 2014 at NMCP and NMCSD. Itineraries limited to western or northern Europe, Canada, or New Zealand were excluded. Travel medicine physicians counseled travelers and provided prescriptions for immunizations, TD self-treatment, and malaria chemoprophylaxis. Counseling was not standardized for this study. Participant demographics, itineraries, vaccinations, and prescriptions were abstracted. Immunizations and prescriptions refused by participants (and reasons for refusal) were not captured. A post-travel survey, completed up to 8 weeks after return, was carried out to collect information on compliance with malaria chemoprophylaxis and personal protective measures, exposures, and occurrence of diarrhea, influenza-like illness or febrile illness. The study was approved by the Uniformed Services University Infectious Disease Institutional Review Board.
Pediatric subjects (aged < 18 years at the time of travel) were matched 1:1 with adult military dependents (i.e., family members of either active duty or retired U.S. military personnel) using the following criteria: 1) geographic region of travel (i.e., Africa, South America/Central America/Caribbean, and Southeast Asia/North Asia/Oceania5); 2) malaria-risk region categorized by the provider as follows: a) none or minimal malaria risk—no chemoprophylaxis indicated, b) chloroquine-sensitive region, c) chloroquine-resistant region, and d) mefloquine-resistant region; and 3) travel duration < 1 or ≥ 1 month.6 We excluded active duty or retired U.S. military personnel because of targeted pretravel care (deployment readiness or military business, respectively) and travelers who visited ≥ 1 geographic region during a single trip. Each subject was included once in the analysis, and pediatric subjects were not matched to adults traveling with them.
Coverage rates and prescription practices for routine and/or travel-related vaccinations were evaluated using the criteria outlined in Table 1.2 Partial or noncompliance with malaria chemoprophylaxis was defined as missing ≥ 2 doses of weekly antimalarials (mefloquine or chloroquine) in a row or ≥ 3 doses of daily antimalarials (doxycycline, atovaquone/proguanil, or primaquine primary prophylaxis) in a row. Definitions for exposures and illnesses are included in Table 2.
Definitions for vaccine indications and up-to-date status
|Category||Vaccination||Indication||Up-to-date status defined as follows|
|Travel vaccinations||Rabies||Travel to regions with risk of rabies transmission (Southeast Asia, South Asia, North Africa, Central America/Caribbean17)||Prior vaccination or provided at pretravel visit|
|Meningococcus||≥ 2 months of age and traveling to African meningitis belt||Prior vaccination ≤ 5 years ago or provided at pretravel visit|
|Yellow fever||≥ 9 months of age and traveling to a yellow fever endemic country (Angola, Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Republic of the Congo, Côte d’Ivoire, Equatorial Guinea, French Guiana, Gabon, The Gambia, Ghana, Guinea, Guinea-Bissau, Guyana, Liberia, Nigeria, Rwanda, Sierra Leone, Senegal, Suriname, Togo, Uganda18)||Any prior vaccination or provided at pretravel visit|
|Japanese encephalitis||≥ 2 months of age and traveling to a Japanese encephalitis endemic country (Cambodia, Indonesia, Thailand, Vietnam, China, Japan, South Korea, Nepal, India, Bangladesh, Brunei, Myanmar, Laos, Malaysia, Papua New Guinea, Philippines, Sri Lanka, Taiwan)||Prior vaccination ≤ 1 year ago or provided at pretravel visit|
|Typhoid||> 2 years of age and traveling to regions with risk of typhoid transmission (Africa, South America/Central America/Caribbean, and Southeast Asia/North Asia/Oceania)||Intramuscular vaccination ≤ 2 years ago or oral vaccination ≤ 5 years ago or prescribed at pretravel visit19|
|Routine vaccinations*||Hepatitis A||Pediatric subjects: all subjects ≥ 1 year of age||Prior vaccination series completion or vaccination prescribed at pretravel visit|
|Adult subjects: subjects traveling to countries with intermediate to high hepatitis A endemicity|
|Hepatitis B||Pediatric subjects: all subjects of any age||Completion of vaccination series before pretravel visit or vaccination prescribed at pretravel visit|
|Adult subjects: subjects traveling to countries with intermediate to high hepatitis B endemicity|
* Advisory Committee on Immunization Practices (ACIP) recommendations for routine hepatitis A and B vaccination of children were issued after subjects in the adult cohort had become adults. ACIP recommends hepatitis A and B vaccination for adults with risk factors for infection, including those traveling to endemic areas. The U.S. Department of Defense requires all active duty military personnel to be vaccinated for hepatitis A and B.
Demographic and trip characteristics of 81 pediatric travelers matched by geographic region of travel, malaria risk at destination, and duration of travel adult military dependents
|Demographic and trip characteristic||Pediatric travelers (n = 81)||Dependent adult travelers (n = 81)||P-value|
|Male, N (%)||40 (48)||6 (7)||< 0.01|
|Nonwhite race, N (%)||46 (57)||26 (32)||0.02|
|Born outside the United Stateds, N (%)||9 (11)||26 (32)||< 0.01|
|Interval between pretravel visit and departure date ≤ 14 days, N (%)||24 (29)||19 (23)||0.45|
|Median trip duration—days (IQR)||16 (11–25)||15 (9–23)||0.65|
|Reason for travel: visiting friends and relatives, N (%)||29 (36)||13 (16)||0.01|
|Exposures, compliance with preventive measures, and illnesses*||Pediatric travelers (n = 48)||Dependent adult travelers (n = 69)|
|Skin exposure†||27 (56)||28 (41)||0.1|
|Animal contact†||19 (40)||14 (20)||0.02|
|Feeding||4 (8)||3 (4)||0.44|
|Hunting/fishing||1 (2)||0 (0)||0.41|
|Riding/touching/petting||16 (33)||11 (16)||0.03|
|Other||1 (2)||4 (6)||0.65|
|Dietary risk behaviors|
|Food prepared by street vendors||37 (82)||49 (75)||0.51|
|Consuming raw foods||30 (67)||36 (55)||0.29|
|Drinking untreated water||7 (16)||18 (28)||0.1|
|Ice in beverages||23 (51)||37 (57)||0.43|
|Mosquito bites reported||33 (69)||30 (44)||< 0.01|
|> 10 mosquito bites||15 (31)||6 (9)||< 0.01|
|Used a skin insect repellent greater than or equal to once/day||33 (69)||30 (45)||0.01|
|Used an insecticide on outer clothing||7 (17)||18 (32)||0.10|
|Used a bed net‡||11/24 (46)||16/32 (50)||0.97|
|Partial or noncompliance with malaria chemoprophylaxis§||3/32 (9)||8/46 (17)||0.64|
|TD‖||7 (15)||15 (22)||0.33|
|Influenza-like illness||4 (8)||12 (17)||0.16|
|Febrile illness||5 (10)||2 (3)||0.12|
TD = traveler’s diarrhea. Statistically significant differences (P < 0.05) are represented in bold.
* Exposures, compliance with preventive measures, and illnesses only evaluated in subjects who completed a post-travel survey.
† Definitions for exposures reported by subjects (or their guardians): Skin exposure: walking barefoot on a rural terrain or beach, or wading in fresh water. Animal contact: close contact with wild or domesticated animals. Insect vectors: mosquito, tick, or other insect bites.
‡ Bed net use reported among those who were recommended a bed net at the pretravel consultation.
§ Partial or noncompliance with malaria chemoprophylaxis reported in those who were prescribed an antimalarial and was defined as missing ≤ 2 doses of weekly antimalarials (mefloquine or chloroquine) in a row or ≥ 3 doses of daily antimalarials (doxycycline, atovaquone/proguanil, or primaquine primary prophylaxis) in a row.
‖ Definitions for travel-related illness: TD: as ≥ 3 unformed stools or two unformed stools with ≥ 1 accompanying symptom (nausea, vomiting, abdominal pain, fever, and blood in stool) within 24 hours. Influenza-like illness: subjective fever associated with either a sore throat or cough. Febrile illness: subjective fever not associated with diarrhea or influenza-like illness.
Statistical analysis was conducted using SAS version 9.4 (SAS Institute, Cary, NC). McNemar’s test was used to assess differences between matched pediatric and adult subjects (α = 0.05). A multivariate Poisson regression with robust error variance was used to evaluate differences in antibiotics and/or antidiarrheal prescriptions for TD self-treatment.
A total of 2,736 DoD active duty service members, retirees, and dependents were enrolled in the study. Of these, 86 children and 786 adult dependents were used to create 81 matched pairs (Table 2). The median age of pediatric subjects was 11 years (IQR: 8–16). Thirty subjects (36%) were < 10 years of age and seven subjects (9%) were ≤ 2 years of age. Most adult dependents were female (93% versus 52% of pediatric subjects). Thirty-one (38%) paired subjects traveled to Southeast Asia/North Asia/Oceania, 30 (37%) traveled to South America/Central America/Caribbean, and 20 (25%) traveled to Africa. Children were more likely to be visiting friends and relatives (VFRs) (36% versus 16% of adult subjects). With respect to malaria-risk region, 26 paired subjects (32%) traveled to a low or non–malaria risk area that did not require chemoprophylaxis, seven (9%) traveled to a chloroquine-sensitive malaria-risk area, 47 (58%) traveled to a chloroquine-resistant malaria-risk region, and one (1%) traveled to a mefloquine-resistant region.
There were significant differences in hepatitis A and B coverage rates between pediatric and adult subjects (Figure 1). Less than 50% of adults and children with potential indications for Japanese encephalitis or rabies vaccination were up-to-date on the series (see Table 1 for definitions). Atovaquone–proguanil was the most commonly prescribed antimalarial (79% [44/56] pediatric subjects and 71% [40/56] adults). Adult subjects received antibiotics (95% versus 77%) and antidiarrheals (e.g., loperamide) (100% versus 41%) for TD self-treatment more frequently than pediatric subjects (P < 0.05 for both comparisons). Further stratified by age, pediatric subjects < 10 years of age were less likely to have received a prescription for antibiotics (60% versus 95%; RR = 0.63; 95% CI: 0.47–0.85) and antidiarrheals (10% versus 100%; RR = 0.10; 95% CI: 0.03–0.30) than adult subjects. A limited number of antidiarrheal prescriptions was also observed in subjects aged ≥ 10 years (59% versus 100%; RR = 0.56; 95% CI: 0.46–0.74) compared with adults.
Forty-eight pediatric travelers and 69 adult travelers completed a post-travel survey (Table 2). The median duration between trip return and completion of the post-travel survey was 23 days (IQR: 10–46 days). Pediatric subjects were more compliant with daily skin insect repellent use, reported mosquito bites more frequently, and were more likely to have been in contact with animals than adult subjects. There were no significant differences in rates of self-reported illnesses.
To demonstrate that our results were not skewed by gender (adult dependents consisted largely of women), we looked at a matched set of active duty personnel and found they were similar with respect to compliance with protective measures and illnesses (Supplemental Table 1).
Pediatric subjects traveled to regions with intermediate or high risk of TD,7 and two-thirds traveled to regions endemic for malaria. Although the study was limited by a relatively small sample size, our results are consistent with prior studies.8,9 Children were more likely to be VFRs than matched adults—an important finding because children with foreign-born parents are more likely to travel before 5 years of age, have longer trip durations, and visit high-risk destinations for yellow fever, malaria, and typhoid, potentially increasing the risk of travel-associated infections.2,8 In addition, a higher proportion of children ≤ 5 years of age presenting for a travel-related illness in the GeoSentinel cohort were VFRs.2 Providing effective pretravel counseling to VFR pediatric travelers with foreign-born parents may be challenging because of language barriers and perceptions regarding the risk of travel-related infections.10
Differences observed in hepatitis A and B coverage rates represent a missed opportunity for catch-up vaccination of adults (Table 1). Approximately 25% of travelers planned to depart within 14 days of the pretravel visit, decreasing the protective efficacy especially in cases with no prior vaccination. We observed low coverage rates in pediatric (12%) and adult (28%) subjects with a potential indication for rabies vaccination. Pediatric subjects reported animal contact at higher rates (40% versus 20% in adults) despite having a relatively short duration of travel (median duration was approximately 2 weeks). Given the risk of animal scratches or bites in young children, and the possibility for caregivers to be unaware of such exposures, pretravel counseling should include the potential benefits of rabies vaccination in short-term pediatric travelers going to endemic countries. We also observed a higher incidence of mosquito bites and higher compliance with repellent use among children, similar to findings in prior studies showing a positive correlation between skin repellent use and mosquito bite frequency.11,12 Pretravel consultations should emphasize the importance of compliance with protective measures as an effective means of preventing both nuisance bites and vector-borne diseases.
Pediatric subjects, especially those younger than 10 years, were less likely to be prescribed antibiotics or antidiarrheal agents for the TD self-treatment than adult subjects despite similar rates of TD risk behaviors and incidence. These results are in line with published data13 and emphasize the need for evidence-based treatment guidelines for pediatric travelers. In adults with moderate or severe TD, antimicrobial agents have been demonstrated to effectively reduce clinical symptoms and shorten the duration of illness to about 1.5 days, and to less than one half day when combined with loperamide.14 Providers must also consider regional differences in pathogen distribution when selecting an antibiotic, as well as the potential for harm due to side effects or acquisition of multidrug-resistant organisms.15,16
This study has several limitations. Our assessment of travel risk and preventive care may not be generalizable to travelers who do not seek pretravel care or are seen by nonspecialized providers. By excluding active duty personnel and retirees, our adult comparator group consisted largely of women. Pediatric subjects had a lower post-travel survey response rate (41%) than adults (85%), likely because adults were required to complete an in-person post-travel study visit for a blood draw with a $50 compensation, which was not performed in children. Other limitations include the potential for recall bias on surveys and the inability to capture additional factors relevant to vaccine administration (e.g., season of travel and exposure risk for Japanese encephalitis vaccine, or vaccine administration outside the military health system).
Our findings demonstrate important differences between adult and pediatric travelers that should be considered during pretravel consultation when prescribing relevant preventive and treatment measures.
National Travel and Tourism Office, 2014. Profile of US Resident Travelers Visiting Overseas Destinations: 2014 Outbound. Available at: http://travel.trade.gov/outreachpages/download_data_table/2014_outbound_profile.pdf. Accessed October 20, 2016.
Hagmann S, Neugebauer R, Schwartz E, Perret C, Castelli F, Barnett ED, Stauffer WM, 2010. Illness in children after international travel: analysis from the GeoSentinel Surveillance Network. Pediatrics 125: e1072–e1080.
Soriano-Arandes A 2016. Travelers’ diarrhea in children at risk: an observational study from a Spanish database. Pediatr Infect Dis J 35: 392–395.
Lalani T 2015. Epidemiology and self-treatment of travelers’ diarrhea in a large, prospective cohort of department of defense beneficiaries. J Travel Med 22: 152–160.
Harvey K, Esposito DH, Han P, Kozarsky P, Freedman DO, Plier DA, Sotir MJ; Centers for Disease Control and Prevention, 2013. Surveillance for travel-related disease–GeoSentinel surveillance system, United States, 1997–2011. MMWR Surveill Summ 62: 1–23.
Waller JL, Brantley VC, Podolsky RH, 2010. Where’s the Match? Matching Cases and Controls after Data Collection. Available at: https://www.lexjansen.com/wuss/2010/HOC/3043_4_HOR-Waller.pdf. Accessed January 7, 2019.
Han P 2012. Health challenges of young travelers visiting friends and relatives compared with those traveling for other purposes. Pediatr Infect Dis J 31: 915–919.
Hendel-Paterson B, Swanson SJ, 2011. Pediatric travelers visiting friends and relatives (VFR) abroad: illnesses, barriers and pre-travel recommendations. Travel Med Infect Dis 9: 192–203.
Heywood AE, Zwar N, 2018. Improving access and provision of pre-travel healthcare for travellers visiting friends and relatives: a review of the evidence. J Travel Med 25: 1–8.
Vickery JP, Tribble DR, Putnam SD, McGraw T, Sanders JW, Armstrong AW, Riddle MS, 2008. Factors associated with the use of protective measures against vector-borne diseases among troops deployed to Iraq and Afghanistan. Mil Med 173: 1060–1067.
Goodyer LI, Croft AM, Frances SP, Hill N, Moore SJ, Onyango SP, Debboun M, 2010. Expert review of the evidence base for arthropod bite avoidance. J Travel Med 17: 182–192.
Hagmann S, LaRocque RC, Rao SR, Jentes ES, Sotir MJ, Brunette G, Ryan ET, 2013. Pre-travel health preparation of pediatric international travelers: analysis from the global TravEpiNet Consortium. J Pediatr Infect Dis Soc 2: 327–334.
DuPont HL, Ericsson CD, Farthing MJ, Gorbach S, Pickering LK, Rombo L, Steffen R, Weinke T, 2009. Expert review of the evidence base for self-therapy of travelers’ diarrhea. J Travel Med 16: 161–171.
Kantele A, Mero S, Kirveskari J, Laaveri T, 2016. Increased risk for ESBL-producing bacteria from co-administration of loperamide and antimicrobial drugs for travelers’ diarrhea. Emerg Infect Dis 22: 117–120.
Strysko JP, Mony V, Cleveland J, Siddiqui H, Homel P, Gagliardo C, 2016. International travel is a risk factor for extended-spectrum beta-lactamase-producing Enterobacteriaceae acquisition in children: a case-case-control study in an urban U.S. hospital. Travel Med Infect Dis 14: 568–571.
Gautret P GeoSentinel Surveillance Network, 2007. Animal-associated injuries and related diseases among returned travellers: a review of the GeoSentinel Surveillance Network. Vaccine 25: 2656–2663.
Jentes ES Informal WHO Working Group on Geographic Risk for Yellow Fever, 2011. The revised global yellow fever risk map and recommendations for vaccination, 2010: consensus of the Informal WHO Working Group on Geographic Risk for Yellow Fever. Lancet Infect Dis 11: 622–632.
CDC, 2012. Vaccine Information Statements–Typhoid VIS. Available at: https://www.cdc.gov/vaccines/hcp/vis/vis-statements/typhoid.html. Accessed January 7, 2019.